“On the basis of the improved clinical efficacy with a manageable safety profile, our findings suggest that buparlisib in combination with paclitaxel could become an important second-line treatment option for patients with recurrent or metastatic squamous cell carcinoma of the head and neck eligible for taxane therapy”, say Lisa Licitra, from Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, and co-workers.

The primary endpoint of PFS was a median of 4.6 months with the buparlisib combination versus 3.5 months with placebo, giving a significant hazard ratio (HR) of 0.65, the BERIL-1 investigators report in The Lancet Oncology.

The key secondary endpoint of overall survival also met prespecified criteria for superiority, at a median of 10.4 versus 6.5 months and a HR of 0.72.

“[T]o our knowledge, this study recorded the longest median overall survival reported so far in the second-line setting, which compares favourably with the overall survival reported with existing first-line standard-of-care treatment (ie, cetuximab, platinum, or fluorouracil triplet)”, the researchers comment.

And there was a significantly higher rate of overall response with buparlisib than placebo, at 39% versus 14%, with complete responses in 4% versus 1% and partial responses in 35% versus 13%.

The disease control rate was comparable in the buparlisib and placebo treatment groups (72 vs 70%) and although the median duration of overall response was shorter in the buparlisib group (4.5 vs 7.1 months), the researchers say the imbalance in responder numbers between the treatment arm “limits any conclusions that can be drawn from these results.”

Forest plot analysis of overall survival suggested that patients with archived SCC tissue negative for human papillomavirus (HPV) derived significant benefit from buparlisib whereas no such relationship was found for HPV-positive individuals, with HRs of 0.61 and 1.63, respectively.

Francis Worden, from the University of Michigan Comprehensive Cancer Center in Ann Arbor, USA, describes this result as “compelling” despite the lack of stratification for HPV status in the study.

“These results provide hope for a patient population with a poor prognosis and who might not respond well to immunotherapy”, he writes in an accompanying comment.

Grade 3 or 4 events occurred in 82% of the 76 buparlisib-treated patients given at least one dose of the drug and 72% of the 78 patients given placebo, most commonly hyperglycaemia (22 vs 3%), anaemia (18 vs 12%) neutropenia (17 vs 5%) and fatigue (8 vs 10%). Treatment was discontinued because of adverse events in 10% and 14% of patients, respectively, and the addition of buparlisib was not associated with increased deterioration of quality of life compared with paclitaxel plus placebo.

There were 15 on-treatment deaths in the buparlisib-treated patients and 17 in the placebo group but most were associated with disease progression and none were linked to treatment, the team adds.

Francis Worden concludes: “Although buparlisib is far from the cure for recurrent or metastatic squamous cell carcinoma of the head and neck, this drug shows notable activity, beyond what we have yet been able to achieve with cytotoxic chemotherapy in the setting of platinum therapy failures in these patients.”